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Oxygen Glucose Deprivation (OGD)/Re-Oxygenation-Induced In Vitro Neuronal Cell Death Involves Mitochondrial Cyclophilin-D/P53 Signaling Axis

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Abstract

Oxidative stress-induced neuronal cell death requires opening of the mitochondrial permeability transition pore. P53 mitochondrial translocation and association with Cyclophilin D (Cyp-D) is required for the pore opening. Here we tested this signaling axis in oxygen glucose deprivation (OGD)/re-oxygenation-induced in vitro neuronal death. Using mitochondrion immunoprecipitation, we found that p53 translocated to mitochondrion and associated with Cyp-D in SH-SY5Y cells exposed to (OGD)/re-oxygenation. Disruption of this complex by Cyp-D inhibitor Cyclosporine A (CsA), or by Cyp-D or p53 deficiency, significantly inhibited OGD/re-oxygenation-induced apoptosis-independent cell death. Conversely, over-expression of Cyp-D in SH-SY5Y cells caused spontaneous cell death, and these cells were more vulnerable to OGD/re-oxygenation. Finally, CsA or Cyp-D RNAi suppressed OGD/re-oxygenation-induced neuronal cell death in primary cultures. Together, our study suggests that OGD/re-oxygenation-induced in vitro cell death involves a mitochondrial Cyp-D/p53 signaling axis.

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Abbreviations

OGD:

Oxygen glucose deprivation

Cyp-D:

Cyclophilin D

CsA:

Cyclosporine A

H2O2 :

Hydrogen peroxide

LDH:

Lactate dehydrogenase

mPTP:

Mitochondrial permeability transition pore

ROS:

Reactive oxygen species

NAC:

n-Acetyl cysteine

GFP:

Green fluorescence protein

MEFs:

Mouse embryonic fibroblasts

ANT:

Adenine nucleotide translocase

VDAC:

Voltage-dependent anion transporter

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Acknowledgments

This research was supported in part by grants from the National Natural Science Foundation of China. Funding recourses have no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Conflict of Interest

There authors have no conflict of interests.

Author information

Authors and Affiliations

  1. State Key Laboratory of Reproductive Medicine, Department of Anesthesiology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, China

    Li-Ping Zhao

  2. Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210024, Jiangsu, China

    Chao Ji

  3. Department of General Surgery, Wuxi People’s Hospital of Nanjing Medical University, No. 299, Qingyang Road, Wuxi, 214023, Jiangsu Province, China

    Pei-Hua Lu

  4. Department of Gastroenterology, Xuzhou Chinese Medical Hospital Affiliated to Nanjing University of Chinese Medicine, Xuzhou, Jiangsu Province, China

    Chen Li

  5. Department of Anesthesiology, Wuxi People’s Hospital of Nanjing Medical University, No 299, Qingyang Road, Wuxi, 214023, Jiangsu Province, China

    Bo Xu & Hong Gao

Authors
  1. Li-Ping Zhao
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  2. Chao Ji
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  3. Pei-Hua Lu
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  4. Chen Li
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  5. Bo Xu
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  6. Hong Gao
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Corresponding author

Correspondence to Hong Gao.

Additional information

Li-Ping Zhao and Chao Ji two authors contribute equally.

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Zhao, LP., Ji, C., Lu, PH. et al. Oxygen Glucose Deprivation (OGD)/Re-Oxygenation-Induced In Vitro Neuronal Cell Death Involves Mitochondrial Cyclophilin-D/P53 Signaling Axis. Neurochem Res 38, 705–713 (2013). https://doi.org/10.1007/s11064-013-0968-5

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  • DOI: https://doi.org/10.1007/s11064-013-0968-5

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